Lithium Hexamethyldisilazide → HCID 59547999, compound

HRID 1946384Notes

Reaction equation

HRID 1946384 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:40])[C:32]3[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=3[F:39])=[N:26]2)=[C:20]([C:41]([F:44])([F:43])[F:42])[CH:19]=1>C1COCC1>[F:38][C:37]1[CH:36]=[CH:35][CH:34]=[C:33]([F:39])[C:32]=1[C:31]([NH:30][C:27]1[CH:28]=[CH:29][N:25]([CH2:24][C:21]2[CH:22]=[CH:23][C:18]([CH2:17][N:2]3[N:3]=[CH:4][CH:5]=[N:1]3)=[CH:19][C:20]=2[C:41]([F:42])([F:43])[F:44])[N:26]=1)=[O:40]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 59547848HCID 59547848, compoundHCID 178418936HCID 178418936, compound3×

Product 1

HCID 59547999HCID 59547999, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 1H-1,2,3-triazole (34 mg, 0.492 mmol, Alfa Aesar) in THF (2 ml) at ambient temperature under nitrogen was added 1.0 M lithium bis(trimethylsilyl)amide in THF (0.5 ml, 0.500 mmol). The resulting yellow cloudy mixture was stirred at ambient temperature for 10 min. To a solution of N-(1-{[4-(bromomethyl)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide (for a preparation see Intermediate 22)(49 mg, 0.103 mmol) in THF (2 ml) at ambient temperature was added a solution of the 1H-1,2,3-triazole anion (0.5 ml, 0.167 mmol). After 1.5 h, a further amount of 1H-1,2,3-triazole anion (0.5 ml, 0.167 mmol) was added to the mixture and stirred overnight. The solvent was removed in vacuo and the residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier (Method B). The solvent was evaporated in vacuo to give the title compound as a colourless gum (1.8 mg); LCMS: (System 4) MH+=463.1, tRET=2.85 min.

Workup

  1. customat ambient temperature
  2. waitAfter 1.5 h
  3. stirringstirred overnight
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in 1:1 MeOH
  6. customDMSO (1 ml) and purified by MDAP on Sunfire C18 column
  7. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-d55c0b15a3a64f27bab3ae2edf0e2c15
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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